A role of RGS proteins in drug addiction

Biochem Pharmacol. 2008 Jan 1;75(1):76-84. doi: 10.1016/j.bcp.2007.07.045. Epub 2007 Aug 11.


The diverse family of Regulators of G protein signaling (RGS) proteins are widely distributed proteins with multiple functions, including GAP activity for heterotrimeric G protein alpha subunits. Three members of the RGS family, RGS9-2, RGS4 and RGSz, have been shown to play an essential modulatory role in psychostimulant and opiate drug actions. Interestingly, these proteins show distinct structure, distribution pattern and cellular localization. In addition, each of these proteins is differentially regulated by drugs of abuse in particular brain networks and appears to modulate distinct signal transduction events. The striatal enriched RGS9 plays a prominent role in opiate and psychostimulant drug reward; RGS4 appears to modulate opiate dependence via actions in the locus coeruleus, whereas RGSz modulates analgesia via activation of the PKC pathway.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Dopamine / physiology
  • Humans
  • RGS Proteins / chemistry
  • RGS Proteins / physiology*
  • Receptors, G-Protein-Coupled / physiology
  • Receptors, Opioid, mu / physiology
  • Substance-Related Disorders / etiology*


  • RGS Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Opioid, mu
  • regulator of g-protein signaling 9
  • RGS4 protein
  • Dopamine